搜索结果：longevity

Experimental evolution studies with Drosophila melanogaster have long played a role in the effort to dissect the genetic basis of aging and longevity. While selection for postponed reproduction reliably extends lifespan, additional phenotypic consequences and the genomic bases of this adaptation remain unclear. Here, we leveraged the highly replicated Drosophila Experimental Evolution Population (DEEP) system to further investigate the relationship between longevity and other life-history traits. Derived from the same wild population, two tenfold-replicated treatments, each with populations derived from two different ancestral backgrounds: a control treatment in a 14-day generation cycle was maintained for 56 generations, and an experimental treatment in a 70-day cycle maintained for 20 generations. Experimental populations evolved to have longer lifespan, delayed development time, increased fecundity, greater stress resistance, and stronger immune defense. Pooled-population genomic data reveal highly convergent allele frequency shifts within treatments, and point to 300 candidate genes underlying differentiated phenotypes. Candidate genes are enriched for functional categories involving neural development and morphogenesis rather than canonical aging or immune defense pathways. These results recapitulate that selection for postponed reproduction drives broad physiological changes and a highly polygenic adaptive response, with an unprecedented level of experimental replication.

Depression in older adults is closely associated with an increased risk of mild cognitive impairment (MCI), yet existing prediction models often rely on cross-sectional data and fail to capture temporal changes in depressive symptoms. This study aimed to develop and validate a transformer-based dynamic prediction model for MCI risk in older adults with depression using longitudinal data. Data were obtained from the China Health and Retirement Longitudinal Study. A total of 2119 older adults with depressive symptoms were included. A sliding-window time-series framework was constructed using longitudinal follow-up data, and 394 key features were retained after feature screening and missing-data processing. An optimized transformer model incorporating dynamic positional encoding, multi-head self-attention, and gated feedforward networks was developed to model temporal associations between depressive symptom trajectories and subsequent MCI risk. Model performance was compared with that of Extreme Gradient Boosting and support vector machine. External validation was further conducted using data from the Chinese Longitudinal Healthy Longevity Survey. On the test set, the optimized transformer model achieved an accuracy of 0.816 and an area under the receiver operating characteristic curve (AUC) of 0.851, outperforming Extreme Gradient Boosting (AUC = 0.807) and support vector machine (AUC = 0.776). The transformer model also showed superior precision (0.892), specificity (0.841), sensitivity (0.801), and F1 score (0.844), indicating a stronger ability to identify high-risk individuals and capture long-term temporal dependencies in depressive symptom patterns. In external validation using the Chinese Longitudinal Healthy Longevity Survey dataset, the model maintained good generalizability, with an F1 score of 0.783 and an AUC of 0.821. The proposed transformer-based dynamic model demonstrated strong predictive performance and generalizability for identifying MCI risk in older adults with depression. By incorporating longitudinal depressive symptom trajectories, this approach provides a potentially useful tool for early screening, risk stratification, and preventive intervention in aging populations.

Plant-derived exosome-like nanoparticles (ELNs) exhibit diverse physiological activities across biological kingdoms. Talinum fruticosum (L.) Juss., known in Okinawa as 'Shibiran', is a traditional edible medicinal plant that is considered a food-based remedy. Okinawa, one of the five globally recognized 'blue zones', is renowned for its longevity and distinctive health practices. In Okinawan culture, the boundary between food and medicine is often blurred, and medicinal plants such as T. fruticosum are regularly incorporated into the daily diet for their health-promoting properties. However, the biological basis of the health benefits remains poorly understood. To assess its potential pharmacological value, ELNs from T. fruticosum (TfELNs) were isolated and characterized, and their key biological activities were examined. TfELNs were isolated from fresh leaves via ultracentrifugation followed by sucrose density gradient centrifugation. Their size and morphology were analyzed using nanoparticle tracking analysis and transmission electron microscopy. Subsequently, anti-inflammatory effects were evaluated in human THP-1 macrophages stimulated with lipopolysaccharide (LPS) using a multiplex cytokine immunoassay. Antioxidant activity was assessed in THP-1 macrophages under hydrogen peroxide-induced oxidative stress, with intracellular reactive oxygen species (ROS) levels measured using a DCFH-DA fluorescence assay. TfELNs were identified as spherical vesicles with typical exosome-like features, and they exhibited no notable cytotoxicity, thus indicating high biocompatibility. Notably, distinct subset-specific bioactivities were observed: The B2 fraction significantly suppressed LPS-induced interleukin-6 (IL-6) production in THP-1 macrophages, whereas the B1 fraction markedly reduced ROS levels under oxidative stress. These results suggested that TfELNs may exert selective anti-inflammatory and antioxidant activities, highlighting their potential utility in managing IL-6-associated inflammatory and oxidative stress-related conditions. These subset-specific activities suggest a unique pharmacological profile of TfELNs that could inspire future therapeutic applications. Furthermore, these findings may partially explain the traditional medicinal value attributed to T. fruticosum and underscore its relevance in the ethnopharmacological context of Okinawan healthy longevity.

In Malawi, childhood pneumococcal conjugate vaccination has not achieved expected herd protection despite the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in 2011. Vaccine efficacy and longevity of protection are crucial in achieving herd protection. We previously found that PCV13 offers immediate protection from experimental pneumococcal carriage in Malawian adults, but of uncertain duration. In this follow-up study, we aimed to evaluate the longevity of protection of PCV13 vaccination against experimental human pneumococcal carriage measured by 1-year post-vaccination homotypic Streptococcus pneumoniae serotype 6B (Spn6B) rechallenge in healthy Malawian adults. We previously conducted a double-blind, parallel-arm, randomised controlled trial investigating the efficacy of PCV13 or placebo against Spn6B carriage in healthy adults (aged 18-40 years) in Blantyre, Malawi. This longitudinal follow-up study re-recruited all eligible participants available at 1 year post-vaccination. Eligibility criteria for participation remained the same as those for the initial trial. Individuals with safety concerns, including those at increased risk of invasive pneumococcal disease or with close contacts at risk, were excluded from study participation. Participants with natural carriage other than Spn6B were included in the study. Participants were rechallenged intranasally with 80 000 colony-forming units of Spn6B per naris. The primary endpoint was experimental pneumococcal carriage, established by culture of nasal wash samples collected at days 2, 7, and 14 after rechallenge, and was assessed in all participants who received the rechallenge inoculation. The original trial was registered with the Pan African Clinical Trial Registry (PACTR202008503507113) and is closed. Participants were re-recruited from May 10, 2022, to Aug 22, 2023. 137 participants (77% male; median age 26 years [IQR 23-29]) were re-recruited (57 PCV13 and 80 placebo) and completed the study protocol. In the log-binomial adjusted model, vaccine protection on the probability of Spn6B carriage following rechallenge was 73% (relative risk [RR] 0·27, 95% CI 0·08-0·98, p=0·047). Previous experimental Spn6B carriage reduced the vaccine protective effect (RR 2·20, 0·85-5·67, p=0·10). The effect of PCV13 vaccination was reduced within previous Spn6B carriers (RR 8·95, 2·27-35·33, p=0·002) and previous natural pneumococcal carriers (RR 14·31, 1·65-124·20, p=0·016). The study indicates that PCV13 vaccination has a role in preventing pneumococcal carriage for at least 1 year, showing strong interactions with natural carriage events. These findings suggest that the inability to achieve herd protection in Malawi is probably due to factors other than the efficacy or duration of protection of the PCV13 vaccine. Wellcome Trust.

This study investigated the annual culling rate and its main causes on dairy farms in the central region of Santa Fe, Argentina. A cross-sectional study was conducted between February and April 2025 on 77 farms located in the central dairy region of Santa Fe province, Argentina (Castellanos and Las Colonias departments). On each farm, an in-person survey was conducted with the farm manager. Information was collected regarding the farm demographics, the number of culls and mortalities and the causes of culling. The average annual total culling rate for pasture-based systems was 22.3% (range: 10-34%), while for confined systems it was 31% (range: 22-54%). The proportion of cows culled in pasture-based systems was 15.6% (range: 2-30%) compared to 23.6% (range: 14-43%) in confined systems. The annual mortality rate in pasture-based systems was 6.7% (range: 2-20%), while in confined systems it was 7.4% (range: 4-17%). The main causes of culling were reproductive problems, udder health issues, hoof diseases, infectious diseases and low milk production. The main causes of mortality on the farms were traumatic injuries, infectious diseases, mastitis and metabolic disorders, among others. Average cow longevity in pasture-based systems was 4.3 (range: 2-9) lactations compared to 2.9 (range: 1.4-4) lactations in confined systems. Productivity, animal welfare and dairy herd longevity are shaped primarily by management practices rather than by production system type alone, and both pasture-based and confined systems can be optimized to achieve sustainable outcomes.

Water Storage Clay (WSC) is promising for soil moisture regulation, yet the pore-structure mechanisms governing its hydrodynamics remain poorly understood. We hypothesize that a hierarchical pore architecture-spanning millimeter-scale, highly connected macropores and micrometer-scale micropores-is the key structural basis for synergistically efficient water absorption and sustained slow release, and that this performance can be tuned by particle size. Verifying this hypothesis is essential for guiding the design of cost-effective, waste-derived soil amendments for water-scarce regions. This study employs integrated Micro-CT-based 3D quantitative analysis and multi-scale experiments to resolve the architecture and function of WSC granules. The material exhibits a bimodal pore network comprising a millimeter-scale backbone for rapid water conveyance and micrometer-scale micropores for interfacial retention. WSC drastically outperformed loess in both unsaturated capillary absorption and saturated water uptake. The pore network exhibited a functional synergy: millimeter-scale macropores enabled rapid water conveyance, while micrometer-scale micropores provided interfacial retention for prolonged, slow release. An intermediate particle size range optimally balanced these dual functions, maximizing both absorption capacity and sustained-release longevity. These findings establish a quantitative link between bimodal pore architecture and synergistic water absorption-release kinetics in WSC, bridging pore-scale materials design and soil hydrological function. The demonstrated structure-performance relationship provides a rational design framework for converting solid wastes into durable, cost-effective soil amendments tailored for water-scarce regions. Future validation at the field scale under diverse soil-climate conditions will be critical for translating this mechanistic understanding into widespread practice.

Research has shown a robust inverse association between maximal aerobic capacity and muscular strength, and lifestyle related diseases and mortality. People with a substance use disorder have a higher prevalence of lifestyle-related diseases and a shorter life expectancy than the general population. There is a paucity in the literature of normative aerobic capacity and muscular strength variables in people with a substance use disorder. The main purpose of this study was to contribute to establish reference values on these key variables for this patient group, and to compare these data to normative values consisting of healthy age matched controls. A total of 179 men and women with diagnosed substance use disorder according to International Classification of Diseases-10 performed a maximal cardiopulmonary exercise test on a treadmill recording maximal oxygen uptake and maximal oxygen pulse, along with a muscular strength test in a hack squat machine assessing maximal leg strength. Patients with substance use disorder generally demonstrated lower- maximal oxygen uptake (⁓ 15%), maximal oxygen pulse (⁓ 10%) and muscular strength (⁓ 30%) across all age groups compared to comprehensive Norwegian and American reference materials of healthy age-matched populations. This could contribute to explain the higher prevalence of lifestyle related diseases and reduced longevity in this patient group.

Molar-incisor hypomineralization (MIH) remains one of the most challenging conditions in pediatric dentistry, with fragile enamel that compromises structural integrity, patient comfort, and the longevity of traditional restorative treatments. The unpredictable bonding to hypomineralized substrates results in frequent restoration failures, reinforcing the need for new approaches. In this opinion piece, we argue that digital dentistry offers promising strategies to improve precision, durability, and patient-centered care in MIH management. Drawing on a clinical case used as a proof of concept to illustrate feasibility, we describe a fully digital workflow including intraoral scanning, CAD/CAM design, and 3D-printed indirect restoration. Digital workflows may also enrich dental education by familiarizing students with emerging technologies. At the same time, we acknowledge key barriers such as cost, accessibility, and the clinician learning associated with digital adoption. Digital solutions hold promise as part of a broader strategy to improve care for patients with MIH.

Modern humans now routinely survive to advanced ages, in far greater proportions than ancestral populations, and thus experience the consequences of molecular pathways optimized for youth yet still active in old age. Natural selection weakens over the course of adulthood, creating a selection 'shadow' in which deleterious late-acting mutations accumulate and alleles with early-life benefits persist despite late-life costs. An evolutionary lens helps us to understand puzzling patterns - from conserved longevity pathways spanning the tree of life to a 100-fold variation in maximum lifespan across vertebrates - and explains why age-related diseases share genetic architectures. Advances in comparative genomics, large-scale human genetic studies and multi-omics ageing biomarkers now enable rigorous testing of evolutionary predictions. This Review integrates evolutionary genetics with molecular mechanisms to clarify why ageing evolves, how it varies across species and individuals, and how these insights can guide healthspan extension.

Landmark epidemiological studies and clinical trials, such as the Seven Countries Study, the Lyon Diet Heart Study, the PREDIMED Study and the CORDIOPREV Study, have shown significant reductions in cardiovascular events in those following the Mediterranean diet (MD). The aim of the present work is to summarize the most robust available evidence and the major biological pathways underlying the protective effects of the MD, with particular emphasis on the role of PAF inhibitors. Mechanistically, MD functions through a complex synergy of antioxidant, anti-inflammatory, and antithrombotic effects that collectively improve lipid profiles, enhance endothelial function, optimize postprandial metabolism and cell membrane signaling, making it a functional model for human longevity. The PAF-Implicated Atherosclerosis Theory has emerged as a key unifying framework, proposing that Platelet-Activating Factor (PAF)-a highly potent lipid inflammatory mediator-plays a central role in the initiation and progression of atherosclerosis. Oxidized LDL promotes the production of PAF and PAF-like lipids, leading to endothelial dysfunction, vascular inflammation, and atherosclerotic plaque formation. Traditional Mediterranean foods are rich in natural PAF inhibitors, particularly the polar lipid fractions of extra virgin olive oil, as well as wine, fish, vegetables, onions, and garlic. Animal studies demonstrate that these compounds can reduce or even regress atherosclerotic lesions, independently of serum cholesterol levels. Human dietary interventions have further shown that MD-based meals and functional foods enriched with PAF inhibitors reduce PAF activity and improve thrombosis-related biomarkers. This mechanistic framework helps explain phenomena such as the "French Paradox" and the cardio-protective effects associated with fish consumption. Moreover, the extraction of PAF inhibitors from Mediterranean food by-products, such as olive pomace, offers promising ecological and economic advantages. Collectively, targeting PAF and increasing dietary intake of PAF inhibitors represent promising strategies for the prevention and management of atherosclerosis and other inflammatory diseases, supporting the view that PAF may function as a major, modifiable risk factor in these conditions.

The gut microbiota represents a complex microbial ecosystem that contributes to host metabolic regulation, immune homeostasis, and intestinal barrier function. Across the lifespan, gut microbial communities exhibit marked taxonomic and functional variation driven by environmental exposures, dietary patterns, medication use, and age-associated immune alterations. These differences are closely linked to chronic inflammatory states and immune dysregulation that accompany aging. This review synthesizes current evidence on age-associated differences in gut microbiota composition and functional capacity, with a focus on microbial traits and metabolic pathways relevant to host-microbe interactions. Pathological aging is frequently associated with reduced microbial diversity, loss of short-chain fatty acid-producing commensal bacteria, and enrichment of opportunistic or pro-inflammatory taxa. In contrast, healthy aging and longevity are commonly associated with more stable, resilient, and metabolically adaptable microbial communities. At the functional level, recurrent alterations in short-chain fatty acid biosynthesis, bile acid transformation, and tryptophan- and choline-related metabolic pathways define conserved features across aging-associated microbial profiles. Across neurodegenerative, metabolic, and cardiovascular conditions, overlapping taxonomic and functional patterns indicate shared microbiota-associated signatures linked to inflammatory states. Advances in metagenomic sequencing, functional annotation, and microbiome-focused biotechnological approaches now enable integrated analysis of microbial structure and metabolic potential. These developments provide a robust framework for identifying reproducible microbiome-based indicators relevant to aging-associated physiological changes and for translating microbiome research into biotechnology-driven applications.

Surface roughness and mechanical performance are critical determinants of the clinical behavior, hygiene, and longevity of denture base materials. This study investigated the influence of two extrusion temperatures-280 °C and 300 °C-on both the surface roughness and compressive strength of ThermoSens thermoplastic polymer specimens over a 7-day immersion period. Surface roughness was evaluated at baseline, 24 h, and 7 days using a contact profilometer, while compressive strength was measured after 7 days following ISO 604 guidelines. Samples processed at 300 °C exhibited a significantly greater reduction in surface roughness over time (28.3%) compared with those processed at 280 °C (18.3%). However, although specimens processed at 300 °C showed a greater percentage reduction, their absolute roughness values remained higher than those processed at 280 °C. Compression testing demonstrated higher strength and modulus values in the 300 °C group (91.6 ± 1.8 MPa; 1887.9 ± 42.3 MPa) compared to the 280 °C group (82.3 ± 2.1 MPa; 1755.4 ± 38.7 MPa). These findings indicate a trade-off between improved mechanical performance at higher processing temperatures and lower surface roughness at lower temperatures, highlighting the need for the careful optimization of processing conditions.

Genomic stability is critical for cellular function; however, in the central nervous system, highly metabolically active differentiated neurons are challenged to maintain their genome over the organismal lifespan without replication. DNA damage in neurons increases with chronological age and accelerates in neurodegenerative disorders, resulting in cellular and systemic dysregulation. Distinct DNA damage response strategies have evolved with a host of polymerases. The Y-family translesion synthesis (TLS) polymerases are well known for bypassing and repairing damaged DNA in dividing cells. However, their expression, dynamics, and role, if any, in enduring postmitotic differentiated neurons of the brain are completely unknown. We show through systematic longitudinal studies for the first time that DNA polymerase kappa (POLK), a member of the Y-family polymerases, is highly expressed in mouse neurons. With chronological age, there is a progressive and significant reduction of nuclear POLK with a concomitant accumulation in the cytoplasm that is predictive of brain tissue age. The reduction of nuclear POLK in old brains is congruent with an increase in DNA damage markers. The nuclear POLK colocalizes with damaged sites and DNA repair proteins. The cytoplasmic POLK accumulates with stress granules and endo/lysosomal markers. Nuclear POLK expression is significantly higher in GABAergic interneurons (INs) compared to excitatory pyramidal neurons and lowest in non-neurons, possibly reflective of the inherent biological differences such as firing rates and neuronal activity. INs associated with microglia have significantly higher levels of cytoplasmic POLK in old age. Finally, we show that neuronal activity itself can lead to an increase in nuclear POLK levels and a reduction of the cytoplasmic fraction. Our findings open a new avenue in understanding how different classes of postmitotic neurons deploy TLS polymerase(s) to maintain their genomic integrity over time, which will help design strategies for longevity, healthspan, and prevention of neurodegeneration.

Seed aging is a critical biological process that leads to progressive loss of seed vigor, thereby constraining germplasm conservation and agricultural productivity. To elucidate the molecular mechanisms underlying this process in grass species, we performed transcriptomic analyses to characterize regulatory networks underlying seed aging in Elymus sibiricus, a dominant forage species on the Qinghai-Tibet Plateau. Seeds were subjected to artificial accelerated aging (45 °C, 80% relative humidity, 1-6 days), followed by physiological evaluation and RNA sequencing. Seed vigor and germination percentage declined markedly with aging, accompanied by extensive transcriptional reprogramming. Integrative analyses identified pyruvate metabolism, MAPK signaling, and peroxisome function as key processes associated with vigor loss during late-stage aging. WGCNA further revealed that genes encoding heat shock proteins and glutathione metabolism-related enzymes were co-localized within the same module, suggesting a possible synergistic role in preserving seed viability during aging. In addition, WRKY24, ARF9, and ARF19 were identified as candidate hub transcription factors. WRKY24 may contribute to aging by modulating antioxidant defense-related genes (e.g., TRX1 and NRPC1), while ARF9 and ARF19 may regulate ROS homeostasis through predicted downstream targets, including FQR1, PER2, MAO1B, ANN5, and MT2B. Together, these findings support a hypothetical regulatory model in which WRKY and ARF transcription factors coordinate redox homeostasis and hormone signaling to regulate seed longevity in E. sibiricus. This study provides a systems-level framework for understanding seed aging in perennial grasses and identifies potential genetic targets for improving seed storability, with implications for germplasm conservation and alpine grassland sustainability.

Human aging is heterogeneous and can be explored through development, physiological aging, and premature accelerated aging. We established human induced pluripotent stem cell (iPSC) models derived from neonatal fibroblasts, peripheral blood mononuclear cells from a healthy 60-year-old donor, and cells from a Hutchinson-Gilford progeria syndrome patient. All lines were generated using Sendai virus reprogramming, validated for pluripotency, tri-lineage differentiation, and genomic stability. This collection provides a unique comparative platform to dissect normal and pathological aging, enabling analyses of youthful resilience, progressive age-related alterations, and premature progeroid hallmarks. Beyond technical validation, these models offer a conceptual framework to identify longevity biomarkers.